CA2475534A1 - Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy - Google Patents
Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy Download PDFInfo
- Publication number
- CA2475534A1 CA2475534A1 CA002475534A CA2475534A CA2475534A1 CA 2475534 A1 CA2475534 A1 CA 2475534A1 CA 002475534 A CA002475534 A CA 002475534A CA 2475534 A CA2475534 A CA 2475534A CA 2475534 A1 CA2475534 A1 CA 2475534A1
- Authority
- CA
- Canada
- Prior art keywords
- dimer
- avidin
- kit
- antibody
- diagnosis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000539 dimer Substances 0.000 title claims abstract 12
- 108090001008 Avidin Proteins 0.000 title claims abstract 10
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 title abstract 4
- 229960002685 biotin Drugs 0.000 title abstract 2
- 235000020958 biotin Nutrition 0.000 title abstract 2
- 239000011616 biotin Substances 0.000 title abstract 2
- 238000011363 radioimmunotherapy Methods 0.000 title abstract 2
- 230000002285 radioactive effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract 5
- 238000003745 diagnosis Methods 0.000 claims abstract 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 2
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical group [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 108010090804 Streptavidin Proteins 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 229940121896 radiopharmaceutical Drugs 0.000 claims 1
- 239000012217 radiopharmaceutical Substances 0.000 claims 1
- 230000002799 radiopharmaceutical effect Effects 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 101000666340 Homo sapiens Tenascin Proteins 0.000 abstract 1
- 238000011319 anticancer therapy Methods 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/66—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells
- A61K47/665—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
- A61K47/6897—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies
- A61K47/6898—Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies using avidin- or biotin-conjugated antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Nanotechnology (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Medical Informatics (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Crystallography & Structural Chemistry (AREA)
- Toxicology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Dimers of avidin and streptavidins (diavidins) are described wherein the linker is suberate, which in turn, is bound to different functional groups ( - NH2 o-COOH) of avidin. As compared to avidin, the diavidins have shown the ability to increase the amount of labelled biotin on the target, when used i n an in vitropretargeting test using supported human tenascin, the biotinylate d anti-tenascin monoclonal antibody (Mab-B), avidin/diavidin, and biotin-3H. T he use of such diavidins is also described in cancer diagnosis and anticancer therapy based on the three-step pretargeted radioimmunotherapy procedure.</S DOAB>
Claims (20)
1. Avidin dimer, in which two molecules of avidin are bound via the -NH2 groups by means of suberate.
2. Avidin dimer, in which two molecules of avidin are bound via the -COOH groups by means of polyethylene glycol with a molecular weight of 3400.
3. Dimer according to claim 1 or 2, wherein the avidin is streptavidin.
4. Pharmaceutical and/or diagnostic composition containing the dimer of any one of claims 1-3.
5. Composition according to claim 4, which can be administered parenterally or locoregionally.
6. Use of the dimer of any one of claims 1-3 for the preparation of medicaments and diagnostic means.
7. Use of the dimer of any one of claims 1-3 for the preparation of a medicament useful in the diagnosis or treatment of pathological conditions of organs or tissues.
8. Use of the dimer of any one of claims 1-3 for the preparation of medicaments or diagnostic means useful for the therapy or diagnosis of tumours.
9. Use of the dimer of any one of claims 1-3 in pretargeting methods using antibodies in vitro.
10. Use of the dimer of any one of claims 1-3 for the preparation of a medicament useful for the treatment of disease using pretargeting methods with antibodies.
11. Use according to claim 10, where said disease is a tumour.
12. Use according to claim 10, where said antibody is an anti-tenascin antibody.
13. Use according to claim 12, where said anti-tenascin antibody is monoclonal.
14. Use according to claim 10, where said medicament is part of a kit which is useful in the diagnosis and treatment of tumours by means of the three-step pretargeting technique.
15. Use according to claim 14, where said kit contains a radiopharmaceutical.
16. Kit for the radiotherapy or diagnosis of tumours, characterised in that at least one of the components of said kit contains a dimer according to claim 1 or claim 2.
17. Kit according to claim 16, for use in the pretargeting technique.
18. Kit according to claim 17, where said pretargeting technique is three-step.
19. Kit according to any one of claims 16, 17 or 18, containing a biotinylated anti-tenascin.
20. Kit according to claim 19, where said antibody is a monoclonal antibody.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM2002A000128 | 2002-03-08 | ||
| IT2002RM000128A ITRM20020128A1 (en) | 2002-03-08 | 2002-03-08 | DIMERI OF AVIDINA EFFECTIVE IN INCREASING THE CONCENTRATION OF RADIOACTIVE BIOTIN IN IMMUNOTHERAPY WITH "PRETARGETING". |
| PCT/IT2003/000135 WO2003075960A1 (en) | 2002-03-08 | 2003-03-06 | Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2475534A1 true CA2475534A1 (en) | 2003-09-18 |
| CA2475534C CA2475534C (en) | 2011-06-14 |
Family
ID=11456156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2475534A Expired - Fee Related CA2475534C (en) | 2002-03-08 | 2003-03-06 | Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US7425317B2 (en) |
| EP (1) | EP1482981B1 (en) |
| JP (1) | JP4362376B2 (en) |
| KR (1) | KR100993626B1 (en) |
| CN (1) | CN1638807B (en) |
| AR (1) | AR038897A1 (en) |
| AT (1) | ATE395937T1 (en) |
| AU (1) | AU2003217467B2 (en) |
| BR (1) | BR0308117A (en) |
| CA (1) | CA2475534C (en) |
| CY (1) | CY1108268T1 (en) |
| DE (1) | DE60321142D1 (en) |
| DK (1) | DK1482981T3 (en) |
| ES (1) | ES2302917T3 (en) |
| HK (1) | HK1078462A1 (en) |
| IT (1) | ITRM20020128A1 (en) |
| MX (1) | MXPA04008639A (en) |
| PL (1) | PL372721A1 (en) |
| PT (1) | PT1482981E (en) |
| SI (1) | SI1482981T1 (en) |
| TW (1) | TWI345982B (en) |
| WO (1) | WO2003075960A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4488746B2 (en) | 2002-02-26 | 2010-06-23 | シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ | Anti-human tenascin monoclonal antibody |
| ITRM20020128A1 (en) * | 2002-03-08 | 2003-09-08 | Sigma Tau Ind Farmaceuti | DIMERI OF AVIDINA EFFECTIVE IN INCREASING THE CONCENTRATION OF RADIOACTIVE BIOTIN IN IMMUNOTHERAPY WITH "PRETARGETING". |
| ITRM20040105A1 (en) * | 2004-02-27 | 2004-05-27 | Tecnogen Scpa | MONOCLONAL ANTI-POCKET HUMAN ANTIBODY. |
| JP2008064475A (en) * | 2006-09-04 | 2008-03-21 | Osaka Univ | High-sensitivity detection method of target substance, detection kit and detector |
| JP2016511747A (en) | 2013-01-04 | 2016-04-21 | マサチューセッツ インスティテュート オブ テクノロジー | Drug delivery to tissues based on nanoparticle surface binding |
| CN105214843A (en) * | 2015-10-20 | 2016-01-06 | 东莞市利发爱尔空气净化***有限公司 | A kind of electrion unit and air purifier |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4687732A (en) * | 1983-06-10 | 1987-08-18 | Yale University | Visualization polymers and their application to diagnostic medicine |
| EP1138334A3 (en) * | 1992-06-09 | 2002-04-03 | Neorx Corporation | Pretargeting methods and compounds |
| US5482698A (en) * | 1993-04-22 | 1996-01-09 | Immunomedics, Inc. | Detection and therapy of lesions with biotin/avidin polymer conjugates |
| ITRM20020128A1 (en) * | 2002-03-08 | 2003-09-08 | Sigma Tau Ind Farmaceuti | DIMERI OF AVIDINA EFFECTIVE IN INCREASING THE CONCENTRATION OF RADIOACTIVE BIOTIN IN IMMUNOTHERAPY WITH "PRETARGETING". |
-
2002
- 2002-03-08 IT IT2002RM000128A patent/ITRM20020128A1/en unknown
-
2003
- 2003-02-27 TW TW092104307A patent/TWI345982B/en not_active IP Right Cessation
- 2003-03-06 AT AT03712655T patent/ATE395937T1/en active
- 2003-03-06 EP EP03712655A patent/EP1482981B1/en not_active Expired - Lifetime
- 2003-03-06 BR BR0308117-6A patent/BR0308117A/en not_active IP Right Cessation
- 2003-03-06 MX MXPA04008639A patent/MXPA04008639A/en active IP Right Grant
- 2003-03-06 WO PCT/IT2003/000135 patent/WO2003075960A1/en active IP Right Grant
- 2003-03-06 PL PL03372721A patent/PL372721A1/en not_active Application Discontinuation
- 2003-03-06 CA CA2475534A patent/CA2475534C/en not_active Expired - Fee Related
- 2003-03-06 KR KR1020047013257A patent/KR100993626B1/en not_active IP Right Cessation
- 2003-03-06 SI SI200331230T patent/SI1482981T1/en unknown
- 2003-03-06 ES ES03712655T patent/ES2302917T3/en not_active Expired - Lifetime
- 2003-03-06 CN CN038046369A patent/CN1638807B/en not_active Expired - Fee Related
- 2003-03-06 US US10/506,159 patent/US7425317B2/en not_active Expired - Fee Related
- 2003-03-06 AU AU2003217467A patent/AU2003217467B2/en not_active Ceased
- 2003-03-06 JP JP2003574233A patent/JP4362376B2/en not_active Expired - Fee Related
- 2003-03-06 DK DK03712655T patent/DK1482981T3/en active
- 2003-03-06 DE DE60321142T patent/DE60321142D1/en not_active Expired - Lifetime
- 2003-03-06 PT PT03712655T patent/PT1482981E/en unknown
- 2003-03-07 AR ARP030100788A patent/AR038897A1/en unknown
-
2005
- 2005-11-18 HK HK05110361.5A patent/HK1078462A1/en not_active IP Right Cessation
-
2008
- 2008-07-03 US US12/216,449 patent/US7807133B2/en not_active Expired - Fee Related
- 2008-08-18 CY CY20081100874T patent/CY1108268T1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20040093067A (en) | 2004-11-04 |
| EP1482981A1 (en) | 2004-12-08 |
| CN1638807A (en) | 2005-07-13 |
| ITRM20020128A1 (en) | 2003-09-08 |
| HK1078462A1 (en) | 2006-03-17 |
| CA2475534C (en) | 2011-06-14 |
| BR0308117A (en) | 2005-01-04 |
| US7425317B2 (en) | 2008-09-16 |
| MXPA04008639A (en) | 2004-12-06 |
| DE60321142D1 (en) | 2008-07-03 |
| KR100993626B1 (en) | 2010-11-11 |
| PL372721A1 (en) | 2005-07-25 |
| US20090010839A1 (en) | 2009-01-08 |
| CY1108268T1 (en) | 2014-02-12 |
| ES2302917T3 (en) | 2008-08-01 |
| CN1638807B (en) | 2010-05-26 |
| ITRM20020128A0 (en) | 2002-03-08 |
| ATE395937T1 (en) | 2008-06-15 |
| TWI345982B (en) | 2011-08-01 |
| EP1482981B1 (en) | 2008-05-21 |
| US7807133B2 (en) | 2010-10-05 |
| US20050106102A1 (en) | 2005-05-19 |
| AU2003217467A1 (en) | 2003-09-22 |
| DK1482981T3 (en) | 2008-09-01 |
| PT1482981E (en) | 2008-07-15 |
| AR038897A1 (en) | 2005-02-02 |
| JP2005529081A (en) | 2005-09-29 |
| WO2003075960A1 (en) | 2003-09-18 |
| AU2003217467B2 (en) | 2008-06-26 |
| SI1482981T1 (en) | 2008-08-31 |
| TW200306207A (en) | 2003-11-16 |
| JP4362376B2 (en) | 2009-11-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130306 |